Alzheimer's disease (AD) represents one of the major health problems of the older population. Progressive memory decline is one of the hallmark clinical features of the disorder, and results in suffering for patients as well as caregivers. No effective treatment is available, and the etiology remains unknown. Preliminary work at our institution has resulted in the identification of a deficient mitochondrial enzyme, cytochrome oxidase (CytOx), in platelets and brain tissue of small samples of patients with AD. CytOx is a complex enzyme within the mitochondrial electron transport chain that is essential to normal neuronal function, and it is hypothesized that this deficiency may represent a biochemical lesion that is specific to AD. Whether this deficiency if fundamentally related to level of dementia and degree of memory disturbance is unknown. The proposed project will include 100 patients with a diagnosis of probable AD, 50 healthy controls, and 50 patients with Parkinson's disease. First, the sensitivity and specificity of CytOx deficiency in AD will be evaluated. Second, we will examine the degree of dementia and level of memory impairment in relation to CytOx levels in the AD and control groups. Additional analyses will focus on the longitudinal changes in CytOx and memory functioning in each of the groups over a two year period in order to examine whether decreases in CytOx values are associated with concomitant changes in cognitive and memory function. Strong relationships between level of cognitive and memory dysfunction and CytOx deficiency are expected. These studies may result in a useful diagnostic test for AD, in addition to enhancing our understanding of memory decline in the disease, and may have further implications for potential treatment avenues in the future.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
1P01AG009417-01
Application #
3802898
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Colorado Denver
Department
Type
DUNS #
065391526
City
Aurora
State
CO
Country
United States
Zip Code
80045
Kozora, E; Filley, C M; Julian, L J et al. (1999) Cognitive functioning in patients with chronic obstructive pulmonary disease and mild hypoxemia compared with patients with mild Alzheimer disease and normal controls. Neuropsychiatry Neuropsychol Behav Neurol 12:178-83
Filley, C M; Cullum, C M (1997) Education and cognitive function in Alzheimer's disease. Neuropsychiatry Neuropsychol Behav Neurol 10:48-51
Miller, S W; Trimmer, P A; Parker Jr, W D et al. (1996) Creation and characterization of mitochondrial DNA-depleted cell lines with ""neuronal-like"" properties. J Neurochem 67:1897-907
Cullum, C M; Filley, C M; Kozora, E (1995) Episodic memory function in advanced aging and early Alzheimer's disease. J Int Neuropsychol Soc 1:100-3
Parker Jr, W D; Parks, J K (1995) Cytochrome c oxidase in Alzheimer's disease brain: purification and characterization. Neurology 45:482-6
England, J D; Ferguson, M A; Hiatt, W R et al. (1995) Progression of neuropathy in peripheral arterial disease. Muscle Nerve 18:380-7
Parker Jr, W D; Mahr, N J; Filley, C M et al. (1994) Reduced platelet cytochrome c oxidase activity in Alzheimer's disease. Neurology 44:1086-90
Parker Jr, W D; Parks, J; Filley, C M et al. (1994) Electron transport chain defects in Alzheimer's disease brain. Neurology 44:1090-6
England, J D; Gamboni, F; Ferguson, M A et al. (1994) Sodium channels accumulate at the tips of injured axons. Muscle Nerve 17:593-8